Doppler imaging detects bacterial infection of living tissue

Abstract

Living 3D in vitro tissue cultures, grown from immortalized cell lines, act as living sentinels as pathogenic bacteria invade the tissue. The infection is reported through changes in the intracellular dynamics of the sentinel cells caused by the disruption of normal cellular function by the infecting bacteria. Here, the Doppler imaging of infected sentinels shows the dynamic characteristics of infections. Invasive Salmonella enterica serovar Enteritidis and Listeria monocytogenes penetrate through multicellular tumor spheroids, while non-invasive strains of Escherichia coli and Listeria innocua remain isolated outside the cells, generating different Doppler signatures. Phase distributions caused by intracellular transport display Lévy statistics, introducing a Lévy-alpha spectroscopy of bacterial invasion. Antibiotic treatment of infected spheroids, monitored through time-dependent Doppler shifts, can distinguish drug-resistant relative to non-resistant strains. This use of intracellular Doppler spectroscopy of living tissue sentinels opens a new class of microbial assay with potential importance for studying the emergence of antibiotic resistance.

Coherent light scattering from cellular dynamics in living tissues

“…Bacterial infection of tissue culture is amenable to study using TDS because of the strong motions of bacteria driven by flagellar motors or by actin polymerization. An initial study of bacterial infection of DLD-1 tissues using TDS found distinct spectral signatures for Escherichia coli (E. coli) relative to Listeria monocytogenes (L. mono) and Salmonella [418]. The baseline and mid-and long-term spectra for infection by E. coli and L. mono are shown in figure 40.…”

Phase-sensitive detection of anomalous diffusion dynamics in the neuronal membrane induced by ion channel gating

“…Anomalous diffusion of biological systems with the memory effect has been widely observed in microscopic to macroscopic scales such as protein molecular dynamics, intracellular dynamics, ionic gating dynamics, immune responses, and cortical networks (Mercik et al 1999, Mercik and Weron 2001, Min et al 2005, Cook et al 2014, Lisowski et al 2015, Han et al 2020, Choi et al 2021b, Dieterich et al 2022. The advantage of studying anomalous diffusion is that such dynamics in various systems with dramatically different scales are often scale invariant that can be expressed as scale-free power-law correlations by the memory effect (Marinari et al 1998, Cavagna et al 2010, Munoz-Gil et al 2021.…”

Exploration for adequate non-diffractive beam generation in dense scattering media

“…Optical sensing methods have been widely developed for biomedical imaging 1 – 3 and environmental measurements 4 – 6 . As an example, optical coherence tomography (OCT) is a non-invasive ophthalmologic diagnostic technique that renders an in-vivo cross-sectional view of the dense scattering media such as biomedical tissues up to a depth of less than 2 mm 7 – 9 .…”